5-159315942-T-G

Position:

• chr5-159315942-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002187.3(IL12B):​c.*159A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,312 control chromosomes in the GnomAD database, including 5,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5870 hom., cov: 33)
  • Exomes 𝑓: 0.24 (6 hom.)
• Consequence: IL12B NM_002187.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.218

Genes affected

IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-159315942-T-G is Benign according to our data. Variant chr5-159315942-T-G is described in ClinVar as [Benign]. Clinvar id is 352569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12B	NM_002187.3	c.*159A>C		3_prime_UTR_variant	8/8	ENST00000231228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12B	ENST00000231228.3	c.*159A>C		3_prime_UTR_variant	8/8	1	NM_002187.3	P1
IL12B	ENST00000696750.1	c.*159A>C		3_prime_UTR_variant	5/5
IL12B	ENST00000696751.1	c.*641A>C		3_prime_UTR_variant, NMD_transcript_variant	7/7
	ENST00000521472.6	n.289+4528T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40196 AN: 152050 Hom.: 5863 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.243 AC: 35 AN: 144 Hom.: 6 Cov.: 0 AF XY: 0.225 AC XY: 18 AN XY: 80

Gnomad4 EAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.264 AC: 40228 AN: 152168 Hom.: 5870 Cov.: 33 AF XY: 0.269 AC XY: 19977 AN XY: 74402

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.287

Alfa AF: 0.215 Hom.: 3859

Bravo AF: 0.281

Asia WGS AF: 0.432 AC: 1497 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3212227; hg19: chr5-158742950;